LX2761 is an orally-delivered small molecule compound that was discovered by our scientists and is designed to inhibit SGLT1 locally in the gastrointestinal tract without any significant inhibition of SGLT2 in the kidney.
We reported top-line data in December 2018 from two Phase 1 clinical trials evaluating the safety, tolerability, pharmacodynamics and pharmacokinetics of LX2761. The Phase 1a trial enrolled five cohorts of healthy volunteers and two cohorts of type 2 diabetes patients in a randomized, double-blind, placebo-controlled, ascending single dose study of daily doses of LX2761. Patients with type 2 diabetes were washed off metformin for three days prior to dosing. LX2761 demonstrated minimal absorption and no systemic effect, with no increase in urine glucose excretion from baseline. LX2761 also reduced postprandial glucose in diabetic patients while increasing plasma levels of glucagon-like peptide-1, or GLP-1, a hormone produced in the small intestine that stimulates insulin secretion and inhibits glucagon secretion. The most common adverse and dose-limiting event was diarrhea.
The Phase 1b trial enrolled 51 patients with type 2 diabetes in a randomized, double-blind, placebo-controlled ascending multiple dose study of daily doses of LX2761, administered as a single dose or twice per day over an 8-day treatment period. Patients were treated with metformin at the time of screening and for the duration of the study. LX2761 showed reduced postprandial glucose, demonstrating delayed and reduced intestinal glucose absorption while increasing plasma levels of GLP-1 with minimal effect on urinary glucose excretion. The most common adverse event was diarrhea.